Cerebral involvement in a patient with Goodpasture's disease due to shortened induction therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Goodpasture's disease is a rare immunological disease with formation of pathognomonic antibodies against renal and pulmonary basement membranes. Cerebral involvement has been reported in several cases in the literature, yet the pathogenetic mechanism is not entirely clear.</p> <p>Case presentation</p> <p>A 21-year-old Caucasian man with Goodpasture's disease and end-stage renal disease presented with two generalized seizures after a period of mild cognitive disturbance. Blood pressure and routine laboratory tests did not exceed the patient's usual values, and examination of cerebrospinal fluid was unremarkable. Cerebral magnetic resonance imaging (MRI) revealed multiple cortical and subcortical lesions on fluid-attenuated inversion recovery sequences. Since antiglomerular basement membrane antibodies were found to be positive with high titers, plasmapheresis was started. In addition, cyclophosphamide pulse therapy was given on day 13. Encephalopathy and MRI lesions disappeared during this therapy, and antiglomerular basement membrane antibodies were significantly reduced. Previous immunosuppressive therapy was performed without corticosteroids and terminated early after 3 months.</p> <p>The differential diagnostic considerations were cerebral vasculitis and posterior reversible encephalopathy syndrome. Vasculitis could be seen as an extrarenal manifestation of the underlying disease. Posterior reversible encephalopathy syndrome, on the other hand, can be triggered by immunosuppressive therapy and may appear without a hypertensive crisis.</p> <p>Conclusion</p> <p>A combination of central nervous system symptoms with a positive antiglomerular basement membrane test in a patient with Goodpasture's disease should immediately be treated as an acute exacerbation of the disease with likely cross-reactivity of antibodies with the choroid plexus. In our patient, a discontinuous strategy of immunosuppressive therapy may have favored recurrence of Goodpasture's disease.</p

The Influence of Tilia tomentosa Moench on Plant Species Diversity and Composition in Mesophilic Forests of Western Romania–A Potential Tree Species for Warming Forests in Central Europe?

Climate change challenges important native timber species in Central Europe. The introduction of non-native tree species originating from warmer climates is one option to make Central European forests compatible to global warming. This, however, requires an assessment of the species’ growth requirements, and of its impact on biodiversity in its native ranges. Silver lime (Tilia tomentosa), a moderately drought-tolerant, thermophilous tree species of South-eastern Europe is considered suitable for the future. Along three elevational transects in western Romania, we assessed the impact of changing climate and local site conditions on the abundance of this tree species and contrasted plant species diversity and composition of lime-dominated forests with mesophytic oak and beech forests. Local site conditions and disturbance histories shaped the distribution pattern of silver lime. When dominant, it reduced plant species diversity within stands due to its dense canopy. For shade-tolerant, mesophytic species, though, lime forests provided an additional habitat and extended their range into warmer environments. Thus, silver lime may have the potential as an admixed tree species forming a transitory meso-thermophilous habitat in the future. At the same time, silver lime may be limited under increasing drought frequency

Current State and Drivers of Arable Plant Diversity in Conventionally Managed Farmland in Northwest Germany

Agricultural intensification has led to dramatic diversity losses and impoverishment of the arable vegetation in much of Europe. We analyzed the status of farmland phytodiversity and its determinants in 2016 in northwest Germany by surveying 200 conventionally managed fields cultivated with seven crops. The study was combined with an analysis of edaphic (soil yield potential), agronomic (crop cover, fertilizer and herbicide use) and landscape factors (adjacent habitats). In total, we recorded 150 non-crop plant species, many of them nitrophilous generalist species, while species of conservation value were almost completely absent. According to a post-hoc pairwise comparison of the mixed model results, the cultivation of rapeseed positively influenced non-crop plant species richness as compared to winter cereals (wheat, barley, rye and triticale; data pooled), maize or potato. The presence of grassy strips and ditch margins adjacent to fields increased plant richness at field edges presumably through spillover effects. In the field interiors, median values of non-crop plant richness and cover were only 2 species and 0.5% cover across all crops, and at the field edges 11 species and 4% cover. Agricultural intensification has wiped out non-crop plant life nearly completely from conventionally managed farmland, except for a narrow, floristically impoverished field edge strip

Two sides of one medal: Arable weed vegetation of Europe in phytosociological data compared to agronomical weed surveys

International audienc

Increased Hydrophobicity at the N Terminus/Membrane Interface Impairs Gating of the Severe Combined Immunodeficiency-related ORAI1 Mutant*

Patients with severe combined immune deficiency (SCID) suffer from defective T-cell Ca2+ signaling. A loss of Ca2+ entry has been linked at the molecular level to single missense mutation R91W in the store-operated Ca2+ channel ORAI1. However, the mechanistic impact of this mutation on ORAI1 function remains unclear. Confocal Förster resonance energy transfer microscopy revealed that dynamic store-operated coupling of STIM1 to ORAI1 R91W was largely sustained similar to wild-type ORAI1. Characterization of various point mutants at position 91 by whole cell patch clamp recordings displayed that neutral or even negatively charged amino acids did not abolish ORAI1 function. However, substitution by hydrophobic leucine, valine, or phenylalanine resulted in non-functional ORAI1 channels, despite preserved STIM1 coupling. Besides conformational constraints at the N terminus/membrane interface predicted for the hydrophobic mutants, additional key factor(s) were suggested to determine ORAI1 functionality. Calculation of the probability for the 1st transmembrane domain and its hydrophobicity revealed a substantial increase for all hydrophobic substitutions that lead to non-functional ORAI1 R91X mutants in contrast to those with hydrophilic residues. Hence, increased hydrophobicity might lead to disrupted permeation/gating, as an ORAI1 channel with increased pore size and R91W mutation failed to recover activity. In conclusion, the increase in hydrophobicity at the N terminus/membrane interface represents the major cause for yielding non-functional ORAI1 channels